Hydrochloric Acid → 3-Cyclohexene-1-carboxylic acid, 6-methyl-, (1R,6R)-rel-

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Reaction Steps

To a cold (0° C.) solution of 7 (103.86 g, 0.286 mol), in 4:1 THF/water (500 mL), was added 30% hydrogen peroxide (160 mL, 1.40 mol), followed by lithium hydroxide (27.4 g, 0.652 mol). The resulting mixture was slowly allowed to warm to room temperature and after 4 h the reaction was complete. The solution was cooled (0° C.) and sodium sulfite (202 g, 1.6 mole) was added. The bulk of the THF was removed in vacuo and the resulting mixture (pH 12-13) was extracted with methylene chloride (5×200 mL) to remove the chiral auxiliary. The combined methylene chloride organics were dried (MgSO4) and the volatiles were removed in vacuo to yield 44.0 g (87% yield) of the recovered benzyloxazolidinone auxiliary. The aqueous layer was acidified to pH 1-2 with 12 M HCl and extracted with ethyl acetate (5×300 mL). The combined ethyl acetate extracts were dried (Na2SO4) and the volatiles were removed in vacuo to yield an oil which was purified by flash chromatography to give a solid (20.2 g, 51% overall yield from 6). The methyl ester of 5 was shown to be at 97% ee on a 30 m Chiraldex column. Rf 0.40 (ethyl acetate/hexane 1:1); m.p. 65-66° C.; 1H NMR (300 MHz, CDCl3) δ 10.2-11.8 (b, 1H), 5.61-5.69 (m, 2H). 2.12-2.33 (m, 4H), 1.89-2.00 (m, 1H), 1.67-1.77 (m, 1H), 1.02 (d, J=6.6, 3H); 13C NMR (75 MHz, CDCl3) δ 182.3, 126.3, 124.5, 46.8, 32.9, 30.3, 28.7, 19.7; MS (EI) m/z 140 (M+, 21), 122 ([M-H2O]+, 16), 111 (14), 95 (100), 79 (75), 67 (49); [α]D−99.0° (c=4.89, CHCl3).

Provenance & Evidence